Stop Air Leak by Talc or Autologous Blood Patch Therapy (STOP)

A Pilot Randomised Study Comparing the Clinical Efficacy of Stopping Air Leak by Talc Pleurodesis or Autologous Blood Patch Therapy in Secondary Spontaneous Pneumothorax

Background: A pilot study to assess the feasibility of a randomisation trial protocol comparing intrapleural talc pleurodesis versus autologous blood patch therapy (ABPT) in patients with secondary spontaneous pneumothorax (SSP) complicated by persistent air leak (PAL). The proposed randomised protocol comparing talc pleurodesis and ABPT will be feasible and acceptable.

Methods: A multi-centre, two-arm, open-label, randomised controlled feasibility study which includes subjects with SSP and PAL persisting for 5 days eligible for intrapleural therapy, with follow-ups till 3 months after hospital discharge. Recruited subjects will be randomised in 1:1 ratio to receive one dose of talc pleurodesis or ABPT.

Discussion: The main outcome is the feasibility of the trial protocol, based on the percentage of eligible patients enrolled, retained to discharge, and completing 3 months of follow-up. Other important outcomes include complete cessation of air leak and successful chest drain removal within 3 days after the intervention, absolute and percentage changes in digitally measured air leak rates, duration of chest drainage, recurrence of ipsilateral pneumothorax, need for additional pleural interventions, safety outcomes such as drain blockage and pleural infection. Feasibility outcomes will be reported as descriptive data. Comparison of outcomes between the two treatment groups will be analysed on an intention-to-treat basis. Safety outcomes will be reported descriptively for each group. The reported estimates of recruitment rates, adherence, follow-up completeness, and variability and event rates for key clinical outcomes will be used, to inform sample size calculations for future studies incorporating the current study design.

Study Overview

• Status: Not yet recruiting
• Conditions: Pneumothorax Spontaneous Secondary
• Intervention / Treatment: Drug: talc powder; Biological: patient's own venous blood

Detailed Description

Pneumothorax, defined as the presence of air in the pleural space, is a common respiratory emergency that often necessitates prolonged hospitalisation. In cases where pneumothorax occurs in the setting of underlying chronic lung diseases (secondary spontaneous pneumothorax, SSP), the clinical course is considerably more severe. SSP patients are typically more hypoxic, more likely to develop persistent air leak (PAL) (exceeding 5-7 days), and experience longer hospital stays with higher in-patient mortality compared to those with primary spontaneous pneumothorax (PSP).

The management of SSP with PAL remains controversial despite its clinical significance. Numerous strategies, including chemical pleurodesis, autologous blood patch therapy (ABPT), implantation of endobronchial valves (EBV), and surgical pleurodesis, are employed in practice. However, many SSP patients are unsuitable for invasive procedures such as EBV placement or surgery, owing to their poor premorbid status. In this context, ABPT and chemical pleurodesis (often using talc) emerge as low-cost, bedside alternatives. Yet, current practices vary widely, and a lack of robust comparative evidence has left clinicians with no definitive guidance regarding the optimal management approach.

Talc pleurodesis, involving the intrapleural instillation of sterile talc powder, is a commonly adopted treatment for SSP with PAL. Retrospective studies indicate that 37.2% to 44.5% of SSP patients undergo chemical pleurodesis, with talc being the predominant agent. Reported treatment success is around 70%, with a median drainage duration of 12 days post-procedure. Adverse events, most notably chest pain affecting roughly one-third of patients, are not uncommon, although more serious complications such as respiratory distress occur in only 1.6% of cases. Nonetheless, these findings are derived from studies with retrospective designs and variable methodologies, limiting firm conclusions on efficacy and safety.

In contrast, ABPT has been proposed as a promising alternative for managing PAL. This technique involves the intrapleural instillation of autologous blood with the aim of sealing the air leak, initially developed for PAL in post-operative pneumothorax. Several small-scale retrospective and prospective studies have suggested that ABPT can achieve cessation in 26% to 91% of cases, with some reports showing 71.7% to 84.0% of patients experiencing complete resolution within five days. Moreover, ABPT appears safe for repeated administration, with adverse events reported at incidences ranging from 0% to 16%. However, the heterogeneous outcomes likely reflect differences in blood dosage, timing of intervention, number of administrations, and varying definitions of PAL among studies.

Given the controversy and the limitations of existing evidence, a multicentre randomised controlled trial (RCT) comparing talc pleurodesis with ABPT is imperative. To achieve this, a pilot study is designed to rigorously address methodological weaknesses by standardising the timing of pleural interventions, employing a digital chest drain system for precise, quantitative measurement of air leak, and adopting unified criteria for treatment success.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Ka Pang Chan, MBChB; Phone Number: +852 3505 2211; Email: chankapang@cuhk.edu.hk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18 years or older
• Radiographically proven pneumothorax and underlying lung disease (either pre-existing or shown in diagnostic imaging at presentation)
• Spontaneous onset of pneumothorax, not related to trauma or iatrogenic procedure
• SSP with air leak persists for ≥3 days after the first radiographic evidence of pneumothorax
• Intend to administer talc or autologous blood patch therapy (ABPT) to stop the air leak as the next step of treatment

Exclusion Criteria:

• A chest drain size smaller than Fr 12
• Bilateral pneumothorax
• Impaired blood clotting, including baseline INR > 1.5, platelet < 150 x 10^9/L, use of therapeutic dose anticoagulant or dual-antiplatelet agents
• Active or recent (within 6 weeks) pleural infection
• Septicaemia or active extrapleural infection (e.g. pneumonia)
• Use of long-term systemic corticosteroids or immunosuppressant
• Previously received talc or ABPT to the ipsilateral pleural space for the current episode of pneumothorax
• Known sensitivity to talc
• Has had a previous pneumonectomy (either on the same or contralateral side)
• Patients who are pregnant or lactating (females of childbearing potential must have a negative pregnancy test before randomisation)
• Expected survival of less than three months from a different pathology to this pneumothorax (e.g. metastatic malignancy)
• Cognitively impaired and physically unable to follow the turning procedure during intrapleural procedure, or at risk of self-removing chest drain
• Inability to give informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: talc pleurodesis; intrapleural instillation of talc slurry	Drug: talc powder; intrapleural instillation of talc slurry
Active Comparator: Autolougs blood patch therapy (ABPT); intrapleural instillation of patient's venous blood	Biological: patient's own venous blood; intrapleural instillation of patient's own venous blood

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of pilot study trial protocol including the following criteria	i. > 50% of eligible patients are successfully randomised, ii. > 95% of randomised participants are retained to discharge, and iii. > 80% of randomised participants complete 3 months of follow-up or death, whichever earlier.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to air leak cessation	Time from study intervention to complete cessation of air leak and successful removal of all chest drain(s) (in hours)	30 days
Length of hospital stay	Length of hospital stay after study intervention (in days)	3 months
Recurrence of pneumothorax	Recurrence of ipsilateral pneumothorax after study intervention	3 months
Complete cessation of air leak	Complete cessation of air leak for more than 24 hours and successful chest drain removal	3 days
Change in air leak	Absolute reduction and percentage change in the average rate of air leak (in mL/min) from randomisation to 3 days after the study interventions	3 days
Time to intervention	Time from randomisation to study intervention (in hours) and proportion of participants receiving the intervention within 24 and 72 hours	72 hours
Need for (unplanned or elective) additional intervention for persistent air leak	The need for additional (unplanned or elective) interventions for persistent air leak, which includes needle aspiration, chest drain insertion, implantation of endobronchial valve, surgery	3 months
Changes in inflammatory markers	Changes in inflammatory markers, including white blood cells and C-reactive protein	3 months
Breathlessness score	Breathlessness by visual analogue scale, score ranges from 0 to 100, with 0 means no breathlessness, and 100 means the worst breathlessness ever	3 months
Pain score	Pain score in visual analogue scale, score ranges from 0 to 10, with 0 means no pain, and 10 means the worst pain ever	3 months
Occurrence of complications	Occurrence of complications, including chest drain blockage, dislodgement, fever, pleural infection / empyema, acute respiratory distress syndrome (ARDS)	3 months
Protocol adherence	Protocol adherence to planned timing of talc pleurodesis and ABPT	3 months
Adverse events	Incidence, severity, and timing of adverse events (AEs) and serious adverse events (SAEs)	3 months

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong
• Investigators: Study Director: David SC Hui, MD, Chinese University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): October 31, 2029
• Study Completion (Estimated): March 31, 2030

Study Registration Dates

• First Submitted: March 8, 2025
• First Submitted That Met QC Criteria: March 12, 2025
• First Posted (Actual): March 19, 2025

Study Record Updates

• Last Update Posted (Actual): September 4, 2026
• Last Update Submitted That Met QC Criteria: September 1, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: talc pleurodesis; Persistent air leak; autologous blood patch therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Respiratory Tract Diseases; Neoplastic Processes; Pleural Diseases; Neoplasm Metastasis; Pneumothorax; Sulfoxides; Sulfur Compounds; Organic Chemicals; Dimethyl Sulfoxide
• Other Study ID Numbers: STOP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No